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Role of cAMP in mediating effects of fasting on dephosphorylation of insulin receptor.

We studied the effect of fasting on phosphotyrosine phosphatase (PTPase) activities in particulate (PF) and cytosolic (CF) fractions of rat adipocytes and liver. PTPase activity was assessed using [32P]tyrosine insulin receptor (IR). In adipocytes, 48 h fasting significantly inhibited PTPase activity. Dephosphorylation of IR by PF and CF PTPases was reduced by 80 and 65%, respectively. Similar reductions of lesser magnitude were observed in fasted rat livers. The effect of fasting was completely reversed by either refeeding or by incubating "fasted" adipocytes for 2 h in tissue culture medium containing 5 mM glucose. Neither 20 mM glucose nor the presence of insulin influenced phosphatase activity. Because fasting is accompanied by elevated protein kinase C (PKC) and adenosine 3',5'-cyclic monophosphate (cAMP) levels, we examined their influence on adipocyte PTPases. Neither activation (1 microM 12-O-tetradecanoylphorbol-13-acetate) nor inhibition (20 microM sphingosine) of PKC affected PTPase activity. In contrast, cAMP (2 mM) significantly inhibited PTPase activity (80% inhibition at 2 h), and its effect was prevented by a cAMP antagonist RpcAMP. Fasting- and cAMP-induced inhibition of PTPase activity was restored by incubating PF with trypsin (4 micrograms/ml for 5 min), which separated the putative inhibitors from the phosphatases. We conclude that fasting-induced inhibition of PTPases is mediated by elevated cAMP levels, most likely by activating phosphatase inhibitors.

Adipose Tissue↗

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting.

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

Adenosine Triphosphate↗

Low-density lipoprotein receptors in rat adipocytes: regulation with fasting.

Adipose tissue metabolism is exquisitely sensitive to caloric intake. With increasing adiposity more triglyceride and cholesterol are stored within increasingly large adipocytes, whereas less triglyceride and cholesterol are stored as the size of the fat cell decreases. A portion of the uptake of cholesterol by adipocytes is mediated by low-density lipoprotein (LDL) receptors. The present studies addressed whether LDL receptors are differentially regulated in adipose tissue and the liver during fasting in the rat. Two days of fasting caused a reduction in body weight with an approximately 40% decrease in the epididymal fat depot and fat cell size. No changes in serum cholesterol were noted, but serum triglycerides fell approximately 55% with fasting. LDL receptors detected by immunoblotting decreased progressively with fasting to levels that were 95% below controls in adipocytes isolated from epididymal fat pads by 2-3 days. In contrast, hepatic LDL receptor expression was unaltered by fasting. After 2 days of fasting, the rate of synthesis of LDL receptors in isolated adipose cells was decreased approximately 35%, whereas levels of LDL receptor mRNA were diminished approximately 55%. It is concluded that the expression of LDL receptors in rat adipocytes is markedly downregulated during fasting through transcriptional and posttranscriptional mechanisms. Furthermore, LDL receptor expression is differentially regulated in adipose tissue and liver during fasting in the rat.

Adipocytes↗

Fasting and decreased B cell sensitivity: important role for fatty acid-induced inhibition of PDH activity.

Fasting inhibits glucose-induced insulin secretion. We investigated the role of a glucose fatty acid cycle for such inhibition and its molecular basis in pancreatic islets from 48-h fasted rats. The fasting-impaired insulin response to 27 mM glucose was restored by 41% with a carnitine palmitoyltransferase I inhibitor, etomoxir. Etomoxir also restored (by 50%) impaired glucose oxidation in islets from fasted rats and increased the ratio of oxidation to glycolytic flux from 33 to 43%. Fasting decreased total pyruvate dehydrogenase (PDH) activity (active, unphosphorylated plus inactive, phosphorylated form) by 29%, as well as the percentage of active form (54 +/- 5 vs. 79 +/- 2% in fed rats, P < 0.001). Fasting increased islet PDH kinase activity as follows: PDH-bound activity by 36% and free (not PDH bound) PDH kinase by 70%. Fasting failed to affect PDH kinase content when assayed by an enzyme-linked immunoabsorbent assay with antibodies raised against 45 kDa PDH kinase alpha-chain. We conclude that fasting impairs B cell function to a major extent through the operation of a glucose fatty acid cycle and that decreased PDH activity resulting from increased specific activity of PDH kinase constitutes an important molecular mechanism.

Animals↗

Effect of fasting on the intracellular metabolic partition of intravenously infused glucose in humans.

The effects of fasting on the pathways of insulin-stimulated glucose disposal were explored in three groups of seven normal subjects. Group 1 was submitted to a euglycemic hyperinsulinemic clamp ( approximately 100 microU/ml) after both a 12-h and a 4-day fast. The combined use of [3-(3)H]- and [U-(14)C]glucose allowed us to demonstrate that fasting inhibits, by approximately 50%, glucose disposal, glycolysis, glucose oxidation, and glycogen synthesis via the direct pathway. In group 2, in which the clamp glucose disposal during fasting was restored by hyperglycemia (155 +/- 15 mg/dl), fasting stimulated glycogen synthesis (+29 +/- 2%) and inhibited glycolysis (-32 +/- 3%) but only in its oxidative component (-40 +/- 3%). Results were similar in group 3 in which the clamp glucose disposal was restored by a pharmacological elevation of insulin ( approximately 2,800 microU/ml), but in this case, both glycogen synthesis and nonoxidative glycolysis participated in the rise in nonoxidative glucose disposal. In all groups, the reduction in total carbohydrate oxidation (indirect calorimetry) induced by fasting markedly exceeded the reduction in circulating glucose oxidation, suggesting that fasting also inhibits intracellular glycogen oxidation. Thus prior fasting favors glycogen retention by three mechanisms: 1) stimulation of glycogen synthesis via the direct pathway; 2) preferential inhibition of oxidative rather than nonoxidative glycolysis, thus allowing carbon conservation for glycogen synthesis via the indirect pathway; and 3) suppression of intracellular glycogen oxidation.

Adult↗

Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P < 0.001), and the levels of counterregulatory factors increased during the fast [P < 0.05; glucagon and free fatty acids (FFA) with a linear increase and epinephrine, norepinephrine, and cortisol with a clear underlying circadian rhythm]. Growth hormone secretion increased from the first to third day of fasting (P < 0.05) but actually decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P < 0.05), whereas no effect of gender on beta-cell polypeptides was observed. A high body mass index resulted in higher insulin and C-peptide levels during the fast (P < 0.05). In conclusion, we have provided reference intervals for glucoregulatory factors during a 72-h fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value in the investigation of hypoglycemic disorders.

Adult↗

Gender differences in lipid and glucose kinetics during short-term fasting.

Data obtained from studies conducted in animal models and humans suggest that gender affects the metabolic response to fasting. However, differences in body composition between males and females confound the interpretation of these studies, because increased adiposity itself alters the metabolic response to short-term fasting. We evaluated whole body lipid and glucose kinetics during basal (14-h fast) and short-term fasting (22-h fast) conditions in six women and six men who were matched for adiposity (24 +/- 2 and 23 +/- 2% body wt as fat, respectively). Substrate kinetics were measured by infusing stable isotope labeled tracers of glucose ([(2)H(2)]glucose) and glycerol ([(2)H(5)]glycerol). Basal glycerol rate of appearance (R(a)) in plasma, an indicator of whole body lipolytic rate, was greater in women than in men (2.1 +/- 0.2 vs. 1.5 +/- 0.1 micromol x kg body wt(-1) x min(-1); P < 0.05). However, the relative increase in glycerol R(a) with continued fasting was blunted in women compared with men (40 +/- 7 vs. 80 +/- 4% increase; P < 0.05), resulting in similar lipolytic rates in both genders at 22 h (2.8 +/- 0.2 and 2.6 +/- 0.1 micromol x kg body wt(-1) x min(-1) for women and men, respectively). In contrast, glucose R(a) was similar in men and women at 14 h (11 +/- 0.6 vs. 12 +/- 0.7 micromol x kg body wt(-1) x min(-1) and 22 h of fasting (9 +/- 0.6 vs 10 +/- 0.6 micromol x kg body wt(-1) x min(-1). These data demonstrate the presence of sexual dimorphism in lipid, but not glucose, metabolism during both basal and short-term fasting conditions.

Adipose Tissue↗

Effect of fasting and refeeding on pancreatic enzymes and secretagogue responsiveness in rats.

Fasting reduced amylase and increased lipase concentrations but did not affect trypsinogen concentrations in the adult rat pancreas. Fasting also decreased the pancreatic contents of trypsinogen and amylase. A decrease in the responsiveness of dispersed pancreatic acini to carbachol was evident after 3 days of fasting but only at high concentrations of secretagogues. Acini regained their responsiveness, and enzyme concentrations returned to normal after refeeding. Serum insulin levels of fasted rats decreased to one-fourth of control levels but rose to normal 24 h after refeeding. Insulin or glucose given alone prevented the increase in lipase after fasting. Both insulin and glucose were needed to maintain the acinar response to secretagogues in fasted rats. Although cholecystokinin restored the protein and trypsinogen content in fasted rats, it did not correct the relative changes in the exocrine enzymes. There are therefore reversible changes in the exocrine pancreas after fasting. Insulin, glucose, and cholecystokinin seem to regulate these changes.

Adenosine Triphosphate↗

Regulation of lipoprotein lipase in adipose and muscle tissues during fasting.

The purpose of this work was to determine the relationship between lipoprotein lipase (LPL) activity and LPL mRNA in muscle and adipose tissue in fed and fasted rats. In control animals, the correlation between enzyme activity and LPL mRNA for adipose tissue, heart, soleus, fast red vastus lateralis, and fast white vastus lateralis muscle was r = +0.97. Twenty-four hours of fasting increased LPL activity 38% in heart, reduced it 59% in adipose tissue, and had no effect on activity in the three skeletal muscles analyzed. At the same time, relative LPL mRNA concentrations were reduced 25% in adipose tissue and elevated in heart, soleus, red vastus, and white vastus muscles when compared with control concentrations. Prolonging the fast to 6 days was accompanied by a 64% reduction in adipose tissue LPL activity and an increase in the activities of slow-twitch soleus (83%) and fast-twitch red vastus lateralis muscles (193%), with no enzyme activity change in heart or white vastus lateralis muscle compared with values obtained from control fed animals. LPL mRNA concentration was reduced 66% in adipose tissue, increased more than twofold in heart, soleus, and white vastus muscle, and increased threefold in red vastus muscle. Changes in relative LPL mRNA concentration in adipose tissue induced by fasting could, in part, be accounted for by the increases seen in total RNA concentration. The relationships between enzyme activity and LPL mRNA in muscle and adipose tissue were r = 0.97 and 0.77 for 1-day and 6-day fasted animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Effects of fasting and hibernation on ion secretion in ground squirrel intestine.

Ground squirrels were used to study the effects of fasting and hibernation on small intestinal secretory function. Muscle-stripped sheets of jejunum set up in flux chambers were challenged with a variety of secretory agonists, and changes in short-circuit current (Isc) were recorded. Mucosal wet weights per centimeter and crypt dimensions were not affected by a 3-day fast in active squirrels, but villus height and area were significantly reduced in hibernators that had not eaten for over 6 wk. Tissue conductance was significantly greater in fasted and hibernating squirrels compared with fed animals. Maximal changes in Isc evoked by electrical stimulation of submucosal neurons, normalized to serosal surface area, were greater in fasted compared with fed or hibernating squirrels. When responses were normalized to crypt area, neurally evoked changes in Isc were greatest in the hibernators. Carbachol and serotonin evoked dose-dependent changes in Isc that were greater in fasted compared with fed squirrels at all concentrations. Histamine (100 microM) and theophylline (1 mM) also produced greater increases in Isc in fasted than in fed squirrels. The results suggest that a 3-day fast, or the extended fast of hibernation, results in enhanced secretory capacity in the ground squirrel jejunum.

Animals↗

Vigilance states and body temperature during the circadian cycle in fed and fasted pigeons (Columba livia).

Fasting induces nocturnal hypothermia in pigeons. Slow-wave sleep (SWS) and paradoxical sleep (PS) are associated with reduced heat production in pigeons. The possibility that fasting-induced nocturnal hypothermia is related to increased SWS and PS was examined by comparing body temperature (Tb) and vigilance states when pigeons were fed and fasted. The results showed that when Tb is decreasing near the beginning of the dark phase, the percentage of total recording time (%TRT) spent in SWS and PS was elevated in fasting due to increased frequency of episodes and increased duration of PS episodes. When Tb was low during the middle segment of the dark phase, SWS was elevated in fasting due to increased episode duration. However, fasting did not alter PS, which increased in %TRT across the segment due to increased episode frequency. When Tb was rising during the final hours of dark, SWS remained elevated in fasting and %TRT in SWS and PS was relatively high. SWS and PS may promote the fasting pigeon's entry into, and maintenance of, nocturnal hypothermia.

Animals↗

Running endurance in 27-h-fasted humans.

Nine male marathon runners were exercised to exhaustion to determine the effects of a 27-h fast on endurance performance. Each subject completed two exercise tests at the same treadmill speed (set at 70% maximal O2 uptake), one following a 27-h fast and one 3 h after a preexercise meal, in random order. Fasting caused a 44.7 +/- 5.8% (SE) decrease in endurance performance (P less than 0.01). Blood, muscle, psychological, and ventilatory data were examined to determine the cause of the decreased performance. Fasting caused significant increases in O2 uptake (9.3 +/- 2.0%), heart rate (8.4 +/- 2.4%), and rating of perceived exertion, ventilation, and psychological fatigue, evident within the first 60 min of exercise. There were no differences in plasma glucose or epinephrine levels. Muscle glycogen degraded at the same rate (0.482 +/- 0.146 vs. 0.470 +/- 0.281 mumol.g-1.min-1 in the nonfasted and fasted tests, respectively) despite lower respiratory exchange ratio and elevated free fatty acid levels, which may partially explain the elevated O2 uptake. Lactate, insulin, and norepinephrine were all increased in the fasted test (P less than 0.05). The increase in norepinephrine (r = 0.79, P less than 0.01), the diameter of type I muscle fibers (r = 0.70, P less than 0.05), and ending insulin levels (r = -0.88, P less than 0.01) were correlated with endurance time in the fasted state. Fatigue in endurance running for 27-h fasted humans appears to be related to a combination of physiological, psychological, metabolic, and hormonal changes.

Adult↗

Changes in regional vascular resistance and blood volume after hemorrhage in fed and fasted awake rats.

To determine whether fasting alters the response of blood flow to hemorrhage, blood flow was measured by radiolabeled microspheres before and after a 20 ml.kg-1.3 min-1 hemorrhage in fed and fasted chronically cannulated male Sprague-Dawley rats. Restitution of blood volume, as determined by dilution of hematocrit, was attenuated in fasted rats, although the responses of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance were not significantly different. Fasting only affected resting blood flow in the bronchial artery and fat and had no effect on resting vascular resistance in any organ studied. In both fed and fasted rats, hemorrhage led to a significant fall in blood flow to the stomach, small intestine, cecum, colon, spleen, pancreas, kidney, bronchial artery, thymus, and muscle and a rise in blood flow to the adrenals. However, fasting did not significantly alter the response of flow or vascular resistance to these organs. Fasting did alter the blood flow response to hemorrhage in bone, fat, and the hepatic artery. These results demonstrate that 24 h of fasting does not affect the responses of blood flow and vascular resistance to hemorrhage in most organs, even though restitution of blood volume is attenuated.

Animals↗

Respiratory gas-exchange ratios during graded exercise in fed and fasted trained and untrained men.

We evaluated the hypotheses that endurance training increases relative lipid oxidation over a wide range of relative exercise intensities in fed and fasted states and that carbohydrate nutrition causes carbohydrate-derived fuels to predominate as energy sources during exercise. Pulmonary respiratory gas-exchange ratios [(RER) = CO2 production/O2 consumption (VO2)] were determined during four relative, graded exercise intensities in both fed and fasted states. Seven untrained (UT) men and seven category 2 and 3 US Cycling Federation cyclists (T) exercised in the morning in random order, with target power outputs of 20 and 40% peak VO2 (VO2 peak) for 2 h, 60% VO2 peak for 1.5 h, and 80% VO2 peak for a minimum of 30 min after either a 12-h overnight fast or 3 h after a standardized breakfast. Actual metabolic responses were 22 +/- 0.33, 40 +/- 0.31, 59 +/- 0.32, and 75 +/- 0.39% VO2 peak. T subjects showed significantly (P < 0.05) decreased RER compared with UT subjects at absolute workloads when fed and fasted. Fasting significantly decreased RER values compared with the fed state at 22, 40, and 59% VO2 peak in T and at 40 and 59% VO2 peak in UT subjects. Training decreased (P < 0.05) mean RER values compared with UT subjects at 22% VO2 peak when they fasted, and at 40% VO2 peak when fed or fasted, but not at higher relative exercise intensities in either nutritional state. Our results support the hypothesis that endurance training enhances lipid oxidation in men after a 12-h overnight fast at low relative exercise intensities (22 and 40% VO2 peak). However, a training effect on RER was not apparent at high relative exercise intensities (59 and 75% VO2 peak). Because most athletes train and compete at exercise intensities >40% maximal VO2, they will not oxidize a greater proportion of lipids compared with untrained subjects, regardless of nutritional state.

Adult↗

Pulmonary responses to acute ozone exposure in fasted mice: effect of leptin administration.

Leptin is a satiety hormone that also has proinflammatory effects, including augmentation of ozone-induced pulmonary inflammation. The purpose of this study was to determine whether reductions in endogenous levels of leptin can attenuate pulmonary responses to ozone. To reduce serum leptin, we fasted mice overnight before ozone exposure. Fasting caused a marked reduction in serum leptin to approximately one-sixth the levels observed in fed mice, and continuous infusion of leptin via Alzet micro-osmotic pumps restored serum leptin to, but not above, fed levels. Ozone exposure (2 ppm for 3 h) caused a significant, approximately 40% increase in pulmonary resistance (P < 0.01) and increased airway responsiveness in fasted but not in fed mice. The increased effect of ozone on pulmonary mechanics and airway responsiveness in fasted mice was not observed when leptin was restored via continuous infusion. Ozone exposure caused pulmonary inflammation, as evident by increases in bronchoalveolar lavage cells, protein, and soluble tumor necrosis factor receptors. There was no effect of fasting status on ozone-induced changes in the bronchoalveolar lavage inflammatory profile, and leptin treatment did not alter these responses. Our results indicate that fasting augments ozone-induced changes in pulmonary mechanics and airway responsiveness in mice. These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation.

Airway Resistance↗

Plasma beta-endorphin during fasting in man.

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.

Adolescent↗

Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease.

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

Adult↗

Relation of fasting insulin to blood pressure and lipids in adolescents and parents.

This study was intended to clarify the relation between fasting insulin, lipids, and blood pressure in adolescents before the onset of hypertension and to examine the association of these data with similar data obtained in their parents. The participants in this study were 183 adolescents 14 to 18 years old (96 girls) completing a 4-year intervention trial and their parents (164 mothers, 122 fathers). Blood pressure was measured twice on the right arm in a seated position using a random-zero sphygmomanometer. Fasting blood samples were obtained for lipid and insulin analyses. Fasting insulin was significantly correlated with systolic blood pressure in the adolescents and also in the parents before and after adjustment for body mass index. Fasting insulin was correlated significantly with levels of cholesterol, triglycerides, and HDL and LDL cholesterol in the adolescents. It was correlated only with triglycerides and HDL-cholesterol in mothers and fathers. After adjustment for body mass index, the correlations between fasting insulin and lipids in the children were not significant. A significant relation was shown between children's systolic blood pressure and mothers' fasting insulin and systolic blood pressure. Significant correlations were found between the children's and fathers' triglycerides and HDL-cholesterol, whereas significant correlations were found for fasting insulin and all lipids between mothers and children, and these remained significant after adjustment for body mass index. These results show (1) a significant relation between fasting insulin and both lipids and systolic blood pressure in adolescents and (2) a significant relation for these factors between adolescents and their parents. Although weight appears to play an important role in this relation during adolescence, genetic and environmental factors other than those mediated via weight may control insulin metabolism within families. The data support a role for studies during early biological development to address these issues.

Adolescent↗